CASPER: A Phase I trial combining calaspargase pegol-mnkl and cobimetinib in pancreatic cancer
Asparagine synthetase (ASNS) catalyzes the biosynthesis of asparagine from aspartate and glutamine. Cells lacking ASNS, however, are auxotrophic for asparagine. Use of L-asparaginase to promote asparagine starvation in solid tumors with low ASNS levels, such as pancreatic ductal adenocarcinoma (PDAC), is a rationale treatment strategy. However, tumor cell resistance to L-asparaginase has limited its clinical utility. Our preclinical studies show that RAS/MAPK signaling circumvents L-asparaginase-induced tumor killing, but L-asparaginase and MEK inhibition potentiated tumor killing; suggesting that this combination may provide meaningful clinical benefit to patients with PDAC. This Phase I trial (NCT05034627) will evaluate the safety and tolerability of the MEK inhibitor, cobimetinib, in combination with pegylated L-asparaginase, L calaspargase pegol-mknl, in patients with locally-advanced or metastatic PDAC.
Authors
- Tasha Gingerich
- Katherine Nelson (ORCID: https://orcid.org/0000-0001-5197-5586)
- Diane Ventura
- Gordon Brent Mills (ORCID: https://orcid.org/0000-0002-0144-9614)
- Shaun M. Goodyear (ORCID: https://orcid.org/0000-0003-0217-0890)
- Anne Fahlman
- Brindha Rajagopalan
- Adel Kardosh (ORCID: https://orcid.org/0000-0002-6241-4896)
- Ze’ev A. Ronai (ORCID: https://orcid.org/0000-0002-3859-0400)
- Bryan R. Foster (ORCID: https://orcid.org/0000-0002-1210-059X)
- Brett C. Sheppard (ORCID: https://orcid.org/0000-0002-2182-7547)
- Brian Brinkerhoff (ORCID: https://orcid.org/0000-0002-6266-7965)
- Alexander R. Guimarães (ORCID: https://orcid.org/0000-0003-4601-9340)
- Exodus Edmerson
- Emerson Y. Chen (ORCID: https://orcid.org/0000-0003-3035-4478)
- Erin Taber
- Preeyam Roy
- Guillaume Joe Pegna (ORCID: https://orcid.org/0000-0002-2754-5065)
- Jonathan R. Brody (ORCID: https://orcid.org/0000-0003-3680-3270)
- Rosalie C. Sears (ORCID: https://orcid.org/0000-0003-1558-2413)
- Dove Keith (ORCID: https://orcid.org/0000-0001-6104-3264)
- Johnson Vo
- Charles D. Lopez (ORCID: https://orcid.org/0000-0002-0921-4932)
- Christopher Lessenich
- Francesca Fennell
- Anna Jackson
- Jeong-Youn Lim
Institutions
- Oregon Health & Science University (US)
- Cancer Institute (WIA) (IN)
- OHSU Knight Cancer Institute
- University of Portland (US)
Publication Details
- Journal
- Future Oncology
- Published
- 2024-10-08
- DOI
- https://doi.org/10.1080/14796694.2024.2395235
- Citations
- 3
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.86
Funders
- Center for Strategic Scientific Initiatives, National Cancer Institute
- Servier
- Genentech